What is Tuberculous Meningitis?
Mycobacterium tuberculosis is a type of bacteria that can cause an infection in the central nervous system (the part of the body which includes the brain and spinal cord). This infection can appear in several ways such as meningitis, tuberculoma, and spinal arachnoiditis. Tuberculous meningitis (or TBM for short) happens when these bacteria spread to the protective layers around the brain or spinal cord, known as the meninges. This causes the meninges to get inflamed.
It’s estimated that about one-third of all people in the world could be infected with Mycobacterium tuberculosis. Unfortunately, the number of people with tuberculosis keeps going up, even with improvements in treatment. This is happening despite the global efforts to make sure everyone can easily access medicine and follow official treatment plans.
What Causes Tuberculous Meningitis?
It’s tough to predict who among those infected with tuberculosis (TB) will go on to develop tuberculous meningitis, a serious brain infection. Children who have TB, especially those under the age of 5, are more likely to develop this infection. This is more common in developing countries, where TB is more widespread among children.
In contrast, in developed countries, this brain infection is usually seen in adults who have a reactivation of their TB. People who have other conditions that affect their immune system, such as long-term use of steroids, diabetes, and chronic alcoholism, also run a similar risk of developing this brain infection.
The highest risk of getting this infection goes hand-in-hand with HIV. Patients with both HIV and TB have been found to be five to ten times more prone to develop a brain disease.
Risk Factors and Frequency for Tuberculous Meningitis
Despite being both preventable and curable, tuberculosis is the leading cause of death worldwide from an infectious disease. It’s estimated that about one-third of the world’s population is infected with the bacteria that causes tuberculosis. Before medicines to treat it were developed, Tuberculous meningitis, a type of tuberculosis, was often fatal. Even now, it’s the leading cause of death and disability in children with tuberculosis. This particular type of tuberculosis can also show up when people with HIV start their treatment if they also have an undiagnosed tuberculosis infection.
- Tuberculous meningitis is found in 1% of all cases of tuberculosis that affect parts of the body other than the lungs.
- In developed countries with a lower number of tuberculosis cases overall, this type affects about 6% of all meningitis cases.
- However, in places with more tuberculosis cases, it can account for up to a half of all cases of bacterial meningitis.
- People with HIV have a five times higher risk of this type of tuberculosis spreading to the nervous system and throughout the body, especially when their CD4 count (a measure of immune system health) is less than 100 cells/microL.
Signs and Symptoms of Tuberculous Meningitis
Tuberculous meningitis, a type of chronic meningitis, can be hard to diagnose because its symptoms are similar to other forms of chronic meningitis. Common symptoms include fever, headache, altered awareness, and specific nerve-related issues such as facial paralysis. The challenging part is that these symptoms can occur anywhere from a few days to six months. The disease progression and symptoms of tuberculous meningitis remain constant, irrespective of whether the patient has HIV or not.
Typically, tuberculous meningitis consists of three main clinical phases:
- The early phase, or prodromal phase, comes on slowly with symptoms like a low-grade fever, general discomfort, headaches, and changes in personality. This phase typically lasts from one to three weeks.
- The second phase, known as the meningitic phase, is marked by prominent neurological symptoms such as prolonged headaches, vomiting, meningismus (a combination of symptoms of meningitis), fatigue, confusion, and varying presentations of cranial nerve and long-tract signs.
- The third phase, the paralytic phase, is when confusion can turn into a stupor, seizures, and coma. It often includes hemiparesis (half of the body’s paralysis). If not treated, death usually happens five to eight weeks from the onset of illness.
Some patients may also display unusual symptoms. These include a rapidly progressing meningitic syndrome, which may suggest bacterial meningitis, slow dementia progression over several months, personality changes, social withdrawal, memory impairments, and decreased sexual desire. In some cases, patients may present an encephalitic course, which is characterized by seizures, stupor, and coma without the clear signs of meningitis.
Testing for Tuberculous Meningitis
To assess for Tuberculous meningitis, which is an infection of the brain’s protective layers caused by tuberculosis bacteria, doctors usually examine the cerebrospinal fluid (CSF). CSF is the clear fluid found in the brain and spine. The test often shows low sugar levels, high protein levels, and a slight increase in white blood cell (WBC) count, with more lymphocytes than usual. Lymphocytes are a type of white blood cell that helps your body fight off infections. The findings in this analysis usually look quite similar to those seen in viral meningitis.
Getting a definitive diagnosis of tuberculosis (TB) is quite difficult, especially in parts of the world where resources are limited. The best way to confirm TB is to identify Mycobacterium tuberculosis bacteria (MTB) in the CSF. Traditional testing methods, which involve looking for these bacteria under a microscope after staining them with a special dye (in a test called Ziehl-Neelsen acid-fast bacilli or AFB), are not always reliable. The chances of finding these bacteria range widely from 0% to 87%. On the other hand, growing these bacteria from the CSF sample in a lab (a process known as “culturing”) gives positive results only 40 to 83% of the time and it could take up to 6 to 8 weeks to get the results. However, if CSF samples are taken daily over several days for testing, the chances of finding these bacteria can increase to over 85%.
There are newer, more advanced tests that look for specific proteins related to TB, using a technique called PCR. However, these tests have not become common because they’re not always available and the results can vary a lot. The preferred method in most cases will depend on what resources are available. Despite the development of newer testing methods, the best way to confirm TB is still to grow the bacteria from the CSF sample in a lab. This method also allows for testing the bacteria’s resistance to drugs, which is essential as drug-resistant TB can cause up to two times higher death rates.
Other tests that can be used include one that detects a specific TB protein in the urine and another which measures the levels of adenosine deaminase, an enzyme that’s often increased in TB.
Since diagnosing tuberculous meningitis is difficult, it often goes unnoticed. This has led to the creation of clinical algorithms, which are guided procedures to help differentiate tuberculous meningitis from other forms of meningitis. These procedures largely depend on CSF test findings and the patient’s symptoms. They look at the duration of the symptoms (whether they’ve been present for 5 days or more), any neurological symptoms, the ratio of sugar levels in the CSF to that in the blood (if it’s less than 0.5), and the CSF protein level (if it’s more than 100 mg/dl). These procedures have been evaluated in several clinical trials. However, these trials have been based on previously recorded patient information and have not been validated in prospective trials, i.e., trials that follow patients over time. Therefore, doctors must remain vigilant based on each patient’s risk factors for TB.
Brain scans can also be helpful in diagnosing tuberculous meningitis. Magnetic resonance imaging (MRI) is usually better than computed tomography (CT) as it gives higher quality images of the brainstem and spine, which can help identify tuberculous meningitis. These scans may show signs like brain tissue damage, brain swelling, or enhancement of the brain coverings. CT scans are best used for ruling out severe complications of tuberculous meningitis like hydrocephalus (a condition where there’s excess fluid in the brain), which might require immediate surgery.
Treatment Options for Tuberculous Meningitis
Tuberculous meningitis is a severe type of tuberculosis that affects the brain. Starting treatment as soon as possible is recommended to improve the patient’s chances of recovery and reduce the risk of serious complications. The standard treatment for this condition involves different types of medication: isoniazid, rifampin, pyrazinamide, and either streptomycin or ethambutol. These medications need to be taken daily for two months. The next stage of treatment is a 7 to 10-month period of taking isoniazid and rifampin.
This plan assumes that the tuberculosis bacteria aren’t resistant to these drugs. This is important because treatment can be adjusted based on the bacteria’s resistance to certain drugs. Unfortunately, it can take months to get the results of these drug sensitivity tests.
When treating children, ethambutol is often replaced with either an aminoglycoside or ethionamide since it’s hard to monitor for a possible side-effect called ethambutol-associated optic neuritis, which can affect the optic nerve in the eye.
If the tuberculosis bacteria are resistant to isoniazid, other medicines, including rifampin, ethambutol, pyrazinamide, and fluoroquinolone, are recommended. In this case, treatment needs to last longer, usually 18 to 24 months, depending on how the patient responds to the treatment, the severity of their illness, and the status of their immune system.
In addition to these medications, corticosteroids can be used to manage tuberculous meningitis. Corticosteroids can help reduce the severe reaction of the immune system which can cause brain tissue damage and swelling (edema). Even though there were initial concerns that corticosteroids might limit the effectiveness of the tuberculosis medications, research has shown that this is not the case. In fact, studies found that corticosteroids can help improve patient outcomes and even reduce the risk of death. It has become common practice to use daily injectable dexamethasone for up to four weeks, followed by an oral reduction dose for the next four weeks.
What else can Tuberculous Meningitis be?
The following conditions could be mistaken for one another due to their similar symptoms. Doctors must consider all these possibilities to make an accurate diagnosis:
- Bacterial meningitis
- Viral meningitis
- Encephalitis (brain inflammation from various causes)
- Intracranial space-occupying lesions (health issues which cause something like a mass to occupy space in the brain, including both infections and non-infections)
- Non-specific viral syndromes (general illnesses caused by viruses)
- Sepsis (a severe infection that spreads throughout the body)
- Acute cerebral vascular accident (sudden loss of brain function due to interruption of blood supply)
- Sympathomimetic syndrome due to drug abuse (a condition caused by abuse of drugs that stimulate the nervous system)
- Delirium associated with urinary tract infection (confusion and reduced awareness of the environment resulting from UTI)
What to expect with Tuberculous Meningitis
Tuberculous meningitis is the most dangerous form of a disease called MTB infection. Even when treated, this condition has a death rate between 20 and 67%, and without treatment, it’s often fatal. Certain people are at higher risk of death from tuberculous meningitis, like those who are very young or very old, and those who also have HIV.
The patient’s chances of getting better or worse (prognosis) depend on several factors. These factors include the severity of the neurological symptoms when they first see the doctor, and how quickly they can start on anti-tuberculous medication. Even those who quickly receive treatment may not fully recover, especially if they develop a condition called hydrocephalus due to MTB infection. Hydrocephalus, which is a build-up of fluid in the brain, can have a poor prognosis despite surgical intervention.
Possible Complications When Diagnosed with Tuberculous Meningitis
Tuberculous meningitis is a serious condition that could result in numerous neurological complications. These issues may be visible at the start of the disease and may persist even after successful treatment.
Here are some notable complications:
- Hydrocephalus is the accumulation of fluid in the brain due to blockages, leading to increased pressure inside the skull.
- Hyponatremia, or low sodium levels due to inappropriate secretion of a hormone that holds back water, is observed in 40 to 50% of patients.
- Tuberculomas might develop not necessarily linked to tuberculous meningitis, and their formation isn’t prevented by additional steroid treatment.
- Vasculitis, or inflammation of the blood vessels, and stroke may occur in 15 to 57% of patients, depending on the type of diagnostic methods used. MRI is more accurate in diagnosing these conditions than a CT scan.
- Seizures, primarily focused in one area, can result from low sodium levels, blockages in the blood vessels, and irritation of the meninges, the protective layers of the brain.
- Permanent vision loss due to pressure on the optic chiasm (the part of the brain where the optic nerves cross) by a swollen ventricle, as the optic chiasm and optic nerve are surrounded by thick, tuberculosis-related fluid buildups.
- Transverse myelitis, which presents as partial paralysis, sensory problems, and urinary retention in the lower limbs.
Preventing Tuberculous Meningitis
The main focus in treating all types of Tuberculosis, commonly known as TB, is ensuring patients regularly take their medicine. Treating TB takes a long time and if patients don’t take their medicine accurately, the illness becomes harder to treat. This can pose a significant risk to public health.
